Sandbox Reserved 973: Difference between revisions
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The pacemaker of the circadian system is the suprachiamastic nucleus (SNC) located in the hypothalamus. This center controls the circadian rhythm through the coordination of peripheric oscillators all over the organism. The mechanisms that occur in the peripheric system are, at a molecular level, very similar to those in the SNC; that is to say a network of transcriptional and translational regulations, creating different loops that take about 24 hours to complete. This circadian cycle regulates many physiologic parameters and coordonates several phenomenon such as sleep period or hormons level.One one the most important protein in this rhythm is the heterodimeric complex CLOCK:BMAL1, which is a transcriptionnal factor responseable for the activation of 2 type of genes; Period(Per1,Per2) and Cryptochrome(Cry1,Cry2), by interacting with the E-box DNA. This is a central mechanism in the circadian cycle regulation as the downstream products PER and CRY can then accumulate and dimerize too, so they can repress transcription of Bmal1 and Clock at night, after they relocated in the cell nucleus, creating an autoregulatory feedback loop. | The pacemaker of the circadian system is the suprachiamastic nucleus (SNC) located in the hypothalamus. This center controls the circadian rhythm through the coordination of peripheric oscillators all over the organism. The mechanisms that occur in the peripheric system are, at a molecular level, very similar to those in the SNC; that is to say a network of transcriptional and translational regulations, creating different loops that take about 24 hours to complete. This circadian cycle regulates many physiologic parameters and coordonates several phenomenon such as sleep period or hormons level.One one the most important protein in this rhythm is the heterodimeric complex CLOCK:BMAL1, which is a transcriptionnal factor responseable for the activation of 2 type of genes; Period(Per1,Per2) and Cryptochrome(Cry1,Cry2), by interacting with the E-box DNA. This is a central mechanism in the circadian cycle regulation as the downstream products PER and CRY can then accumulate and dimerize too, so they can repress transcription of Bmal1 and Clock at night, after they relocated in the cell nucleus, creating an autoregulatory feedback loop. | ||
On the other hand, CLOCK:BMAL 1 is also able the transcription of retinoic acid-related nuclear receptors: Rev-erbα and Rorα.These proteins have the ability to regulate the transcription of Bmal1, RORα as an activator and REV-ERBα as a repressor. | On the other hand, CLOCK:BMAL 1 is also able the transcription of retinoic acid-related nuclear receptors: Rev-erbα and Rorα.These proteins have the ability to regulate the transcription of Bmal1, RORα as an activator and REV-ERBα as a repressor. | ||
But this molecular clock is also regulated by post-translational modifications of the subunits, notably phosphorylation and ubiquitination. Some modifiers proteins can modify the stabibility or influence the translocation of some core clock actors, including BMAL1 and CLOCK. That's the case of 2 types of Casein kinase 1 (CK1). The mutation of these modifiers can shorten the circadian cycle of the mamals and cause serious sleep disorders. | |||
The two peptides involved in the dimere have very similar sequences. Chez ''mus musculus''BMAL1 is 387 residues long when CLOCK is 361. | The two peptides involved in the dimere have very similar sequences. Chez ''mus musculus''BMAL1 is 387 residues long when CLOCK is 361. | ||
